Recent studies have shown that the expression of limited set of genes is sufficient to induce pluripotency in adult cells (Takahashi et al., 2007 Cell 131: 861-872; Yamanaka, 2009 Cell 137: 13-17). Pathways that regulate stemness in embryonal stem (ES) cells or induced pluripotent stem (IPS) cells also bear striking resemblance to those in cancer (Utikal et al., 2009 Nature 460: 1145-1148; Krizhanovsky et al., 2009 Nature 460: 1085-1086; Wang et al., 2008 Cell 2: 297-299). Subsets of tumor cells expressing genes associated with pluripotency in ES cells have been implicated in the clonogenicity of human tumors and activation of ES-associated genes correlates with adverse outcome in several tumors (Ben-Porath et al., 2008 Nat Genet 40: 499-507; Glinsky 2008 J Clin Oncol 26: 2846-2853; Schoenhals et al., 2009 Biochem Biophys Res Common 383: 157-162). Both ES and IPS cells have considerable promise toward regenerative medicine (Yamanaka, 2009 Cell 137: 13-17). However, immunogenicity and tumorigenicity of these cells represent major potential challenges for effective translation of these approaches in the clinic (Yamanaka, 2009 Cell 137: 13-17, Knoepfler, 2009 Stem Cells 27: 1050-1056; Lui et al., 2009 Curr Stem Cell Res Ther 4: 70-80).
OCT4 forms part of the core transcriptional network of human ES cells and regulates the induction of pluripotency in adult cells (Boyer et al., 2005 Cell 122: 947-956). The capacity of the human immune system to recognize this critical stem-cell gene is not known, but has potential implications for the emerging clinical applications involving therapeutics with ES/IPS-derived cells, or immune-based targeting of stem-cell pathways in cancers, and in particular germ-cell tumors (GCTs).